Dysmorphia
Dysmorphology Dysmorphology: '''the evaluation, diagnosis and study of birth defects or birth defect syndromes '''Etiology of Dysmorphia: '''teratogenic, genetic, multifactorial, etc. '''Major Birth Defect: '''a defect present at birth which has cosmetic, medical, or surgical significance '''Types * Malformation = primary defect arising from poor formation of tissue * Disruption = secondary defect caused by breakdown of normal tissue * Deformation = secondary defect caused by external forces on normal tissue * Dysplasia = primary defect due to abnormal cellular organization within a specific tissue * Syndrome = pattern of abnormalities which occur together from a single cause * Sequence = series of defects secondary to a single localized abnormality in early development * Complex = abnormalities of different structures which arose in the same embryonic region * Association = nonrandom occurrence in two or more individuals of multiple, idiopathic anomalies of blastogenesis Minor Anomalies * <4% of population * no medical, cosmetic, nor surgical significance * Associated Risk of Major Malformation ** 1 minor anomaly = 3.7% risk of MM ** 2 minor anomalies = 6.7% risk of MM ** 3 minor anomalies = 19.6% risk of MM Frequency of Birth Defects * ~2% of newborns * ~4% of toddlers * 6-8% of school-age Birth Defect Associations * Low Birth Weight ** <1500 gm = 16.2% risk of BD ** 1500-1900gm = 13.2% risk of BD ** >4000gm = 2.8% risk of BD * Twinning * Males > Females * Consanguinity Dysmorphology Evaluation * Medical History ** Pregnancy: exposures, obstetric issues, prenatal testing ** Delivery/Newborn Period: type of delivery, birth stats, complications, feeding ** Infancy/Childhood: growth and development, hospitalizations, surgeries, illness, lab data * Family History ** Siblings, parents, consanguinity, ethnicity; recurrent miscarriages, stillborns, neonatal deaths; birth defects ** Negative Family History does ''not ''negate risk of genetic cause ** Presence of similarly affected males relatives of a male child suggests X-Linked Inheritance ** Similar Features in parents/child = benign familial resemblance or undiagnosed parent * Physical Examination ** Growth = use appropriate growth curves for gender, ethnicity, condition ** Note Major & Minor anomalies; normal variants ** Measurements = abnormal is >2 SD above or below the mean *** Head: size, shape, symmetry, face size, shape, hairlines *** Eyes: slant, size, placement, epicanthal folds, eye size, inner/outer canthal, interpupillary distance *** Nose: length, bridge, nares, columella *** Ears: shape, size, location, earlobe creases, preauricular pits / tags *** Mouth: vermillion, shape, dentition, palate, uvula, lip pits *** Philtrum: flat vs grooved, size *** Chin: prognathia, micrognathia, retrognathia *** Neck: length, webbing, lesions, thyromegaly, adenopathy, branchial cleft *** Chest: symmetry, shape, size, heart *** Skin/Hair: skin pigmentation, skin lesions, hair distribution, hair pigmentation *** Extremities: symmetry, size, fingers, palms, toes, soles, flat/arched * Assessment ** Compare to other relatives ** Certain anomalies have better predictive value ** Concentrate on most unusual feature * Laboratory Evaluation ** Blood, Skin, Buccal Cells *** Karyotype **** trisomies **** mosaicism *** Microarray (CGH) **** particular pattern of anomalies **** ambiguous genitalia **** developmental delay +/- major/minor anomalies **** child with 2 single gene disorders **** history of recurrent miscarriages *** FISH/MLPA **** testing for specific disorders *** DNA Testing **** Single gene disorder **** Fragile X **** Uniparental Disomy **** X-inactivation **** Methylation Studies **** Whole Exome Testing *** Metabolic Studies **** amino acids, organic acids, lactate, pyruvate, ammonia, glucose **** testing only if metabolic disorder suspected *** Radiography **** delineation of particular skeletal dysplasia **** determine bone age ***** delayed = hypopituitarism ***** advanced = overgrowth syndromes *** Ophthalmology Evaluation **** Corneal Clouding? Iris Anomalies? Retinal Abnormalities? Visual Acuity? *** Biopsies **** Skin = ultrastructural analysis, inclusions, collagen studies **** Nerve = inclusions **** Muscle = ultrastructural analysis, mitochondria **** Liver = ultrastructural analysis, mitochondria * Follow-Up/Counseling/Management ** Diagnosis may become apparent with age ** Natural history of disease with appropriate screening ** Counseling about genetics, recurrence, prognosis ** Prenatal diagnosis options ** Treatment, if any List of Dysmorphic Features * micrognathia * cleft lip & palate * broad toes * ptosis * craniosynostosis ** scaphocephaly/dolichocephaly ** trigonocephaly ** turricephaly ** brachycephaly * upslanted eyes * downslanted eyes * blepharophimosis * hypertelorism * hypotelorism * microcephaly * macrocephaly * micropthalmia * microstomia * macroglossia * thin vermillion border * preauricular tags, pits * flat philtrum * rectangular nose * bulbous nose * small ears * low-set ears * long palpebral fissures * bifid uvula * velopharyngeal insufficiency * retrognathia * prognathia * midface hypoplasia * small nose * flat nasal bridge * neck webbing * pectus carinatum * pectus excavatum * cafe-au-lait spots * pigmented nevi * temporal balding * hypertrichosis * hemihypertrophy * brachydactyly * clinodactyly * arachnodactyly * polydactyly * syndactyly * pes planus * pes cavum * sandal foot * rocker-bottom feet * single palmar crease (Simian crease) * malformed ears * branchial cleft * lip pits * palmar pits * hypoplastic nails * earlobe creases * round face * long face * bifid ribs * shield chest * bell-shaped chest * prominent glabella * short stature * tall stature * gynecomastia * male with female body habitus * cryptorchidism * macroorchidism * triangular face * shortened proximal limbs * absent muscle * prominent lips * periorbital fullness * brushfield spots * stellate irides * _genitalia ambiguous genitalia * tapered fingers * hypogonadism Syndromes/Conditions With Generalized Dysmorphia * Tetrasomy 12p * Ring X Syndrome * Maternal UPD14 * Brancho-oculo-facial Syndrome * Coffin-Lowry Syndrome